Stroke is a leading cause of long-term adult disability. Due to abnormal timing and magnitude of muscle activation, and altered muscle force generating capacity, performance of gait is disrupted and asymmetric kinematics and kinetics emerge. The proposed work will investigate the relationship between altered muscle morphology, muscle activation, and muscle coordination following stroke. Our technical objectives include the development and implementation of tools to facilitate the creation of subject-specific simulations of human movement using the SimTK framework introduced by the Simbios investigators. We propose to apply this simulation toolkit to understand muscle coordination in post-stroke hemiparesis by achieving the following specific aims: (1) Identify morphological characteristics of paretic and non-paretic muscles in chronic stroke and differences with healthy age- matched subjects, (2) Determine whether reductions in muscle force and net joint torque following stroke are due to altered morphology or impaired activation, (3) Identify factors that limit gait speed in persons post-stroke, and (4) Identify differences between self-selected and fastest possible gait speed for healthy persons and those post-stroke. In the proposed series of studies, static MRI will be used to assess physiological cross-sectional area of key lower extremity muscles. Measurements of muscle activity and net joint torque will be taken during a range of isometric and isokinetic dynamometer tasks. Experimental gait data will be collected on healthy and post-stroke individuals and used to generate subject-specific simulations. A variety of analysis techniques will be employed to assess differences between groups, such as muscle excitation patterns, limb configuration, and the potential effect of muscle forces on joint accelerations, and to address clinically relevant hypotheses. PUBLIC HEALTH RELEVANCE: Stroke is a leading cause of long-term adult disability. The relationship between altered muscle force- generating capacity, activation and coordination during walking after stroke is unclear. Through coupled experiments and simulations, we can identify factors that limit gait speed post-stroke and assist rehabilitation professionals in designing treatment interventions that address the specific impairments of an individual subject. [unreadable] [unreadable] [unreadable]